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STUDY OBJECTIVE To evaluate the intraoperative effects of gonadotropin-releasing hormone (GnRH) analogue pretreatment in patients undergoing cold loop hysteroscopic myomectomy. DESIGN Randomized controlled trial (Canadian Task Force classification I). SETTING Arbor Vitae Center for Endoscopic Gynecology, Rome, Italy. PATIENTS A total of 99 patients were randomized and subsequently allocated to the GnRH analogue group or to the nonpharmacologic treatment control group. Fifteen patients were lost after allocation, and 42 patients per group underwent hysteroscopic myomectomy. INTERVENTIONS Cold loop hysteroscopic myomectomy. MEASUREMENTS AND MAIN RESULTS The control group accomplished the treatment in a 1-step procedure more frequently than the GnRH analogue group (92.85% and 73.8% of cases, respectively; p = .040). The completion of the treatment was more unlikely in case of G2 myomas (p = .006), whereas no differences were recorded for G1 and G0 myomas. The multivariate analysis showed a significant correlation between the multiple-step treatment and the use of GnRH analogue (odds ratio, 5.365; 95% confidence interval [CI], 1.018-28.284; p = .048), grading (odds ratio, 4.503; 95% CI, 1.049-19.329; p = .043), and size of myomas (odds ratio, 1.128; 95% CI, 1.026-1.239; p = .013). CONCLUSIONS Preoperative GnRH analogue administration did not facilitate the completion of cold loop hysteroscopic myomectomy in a single surgical procedure in G2 myomas and was correlated with a longer duration of the surgery. No significant benefits were found for G0 and G1 myomas. (ClinicalTrials.gov: NCT01873378.).